ArticleeLife2016
A Dynamic molecular basis for malfunction in disease mutants of p97/VCP.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.Research square · 2026Article
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.bioRxiv : the preprint server for biology · 2026Article
- The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP.bioRxiv : the preprint server for biology · 2026Article
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.bioRxiv : the preprint server for biology · 2025Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- Allosteric activation of VCP, an AAA unfoldase, by small molecule mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Analysis of the Conformational Landscape of the N-Domains of the AAA ATPase p97: Disentangling the Continuous Conformational Variability in Partially Symmetrical Complexes.International journal of molecular sciences · 2024Article
- Characterizing ATP processing by the AAA+ protein p97 at the atomic level.Nature chemistry · 2024Article
- The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions.Nature structural & molecular biology · 2023Article
- Structural insights of the p97/VCP AAA+ ATPase: How adapter interactions coordinate diverse cellular functionality.The Journal of biological chemistry · 2023Review
- Structural basis of ubiquitin-independent PP1 complex disassembly by p97.The EMBO journal · 2023Article
- The UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPase.Nature communications · 2023Article
- Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases.Biomolecules · 2023Review
- Selenoprotein S: A versatile disordered protein.Archives of biochemistry and biophysics · 2022Review
- Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR.Nature communications · 2022Article
- Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy.International journal of molecular sciences · 2022Review
- Probing allosteric interactions in homo-oligomeric molecular machines using solution NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dissecting the role of interprotomer cooperativity in the activation of oligomeric high-temperature requirement A2 protein.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
p97/VCP is an essential, abundant AAA+ ATPase that is conserved throughout eukaryotes, with central functions in diverse processes ranging from protein degradation to DNA damage repair and membrane fusion. p97 has been implicated in the etiology of degenerative diseases and in cancer. Using Nuclear Magnetic Resonance spectroscopy we reveal how disease-causing mutations in p97 deregulate dynamics of the N-terminal domain that binds adaptor proteins involved in controlling p97 function. Our results provide a molecular basis for understanding how malfunction occurs whereby mutations shift the ADP-bound form of the enzyme towards an ATP-like state in a manner that correlates with disease severity. This deregulation interferes with the two-pronged binding of an adaptor that affects p97 function in lysosomal degradation of substrates. Subtle structural changes propagate from mutation sites to regions distal in space, defining allosteric networks that facilitate inter-domain communication, with potential implications for modulation of enzyme activity by drug molecules.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.